U.S. patent number 3,877,463 [Application Number 05/376,066] was granted by the patent office on 1975-04-15 for thermal method and device for the differential diagnosis of human tumors and circulatory disorders.
This patent grant is currently assigned to Massachusetts Institute of Technology. Invention is credited to John D. Cary, Borivoje B. Mikic.
United States Patent |
3,877,463 |
Cary , et al. |
April 15, 1975 |
Thermal method and device for the differential diagnosis of human
tumors and circulatory disorders
Abstract
The thermal analysis method includes controlled cooling of the
surface of skin tissue and measurement of the surface temperature
difference between cooled cancerous and similarly cooled healthy
tissue. The device which utilizes the effect of local skin cooling
to diagnose the presence of tumors includes a heat sink, a thermal
resistance which maximizes the skin temperature difference between
cancerous and healthy tissue, and a heat collecting disk containing
a temperature sensing device. During diagnostic examinations, the
heat collecting disk is placed upon an area of skin where a tumor
is suspected and upon a contra-lateral area of normal skin. The
skin temperature difference observed by use of the device indicates
blood perfusion changes between the two areas, which for the
identical cooling conditions used, reflects morphological changes
in the tissue. Perfusion rate differences between cancerous and
healthy tissue are indicated by skin temperature differences of up
to 10.degree.C under conditions of strong cooling. For small
superficial tumors of 1 cm.sup.3 volume, temperature differences of
a few degrees centrigrade will be observed with strong cooling. The
method and device can also be used for the detection of various
circulatory disorders.
Inventors: |
Cary; John D. (Brookline,
MA), Mikic; Borivoje B. (Cambridge, MA) |
Assignee: |
Massachusetts Institute of
Technology (Cambridge, MA)
|
Family
ID: |
23483565 |
Appl.
No.: |
05/376,066 |
Filed: |
July 2, 1973 |
Current U.S.
Class: |
600/549;
374/43 |
Current CPC
Class: |
A61B
5/01 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); A61b 005/00 () |
Field of
Search: |
;128/2H,2N,2R,399-403
;73/341,342,19R,15R,15A |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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|
|
|
|
|
127,358 |
|
Nov 1958 |
|
SU |
|
130,151 |
|
Jun 1959 |
|
SU |
|
Other References
Gundersen, "A Versatile Therm. Amp. for Recording of Temp.," Med.
and Biol. Eng'r., Vol. 10, pp. 564-566, 1972. .
"Tumor Temp. Monitoring...For Breast Cancer," Gillespie, Bio.-Med.
Eng'r., Aug. 1971, pp. 358-362, Vol. 6, No. 8..
|
Primary Examiner: Gaudet; Richard A.
Assistant Examiner: Cohen; Lee S.
Attorney, Agent or Firm: Smith, Jr.; Arthur A. Santa; Martin
M. Lorusso; Anthony M.
Government Interests
The invention herein described was made in the course of work
performed under a grant from the National Institutes of Health.
Claims
We claim:
1. A device for determining the perfusion rate of superficial skin
tissue by measuring the temperature of skin after the superficial
tissue has been cooled below its normal temperature comprising:
a flat heat collecting surface having a defined area which can be
placed in thermal communication with the skin and enable heat
transfer from the skin to said heat collecting surface;
a heat sink means for cooling said heat collecting surface to
enable the superficial tissue to be cooled below its normal
temperature when said heat collecting surface is placed in thermal
communication with the skin;
a thermal resistance connected between said heat collecting surface
and said heat sink means including spacer means for defining the
height of said thermal resistance, said heat sink means cooling
said heat collecting surface through said thermal resistance to a
temperature above the value of the heat sink means at steady state;
and,
means for measuring the temperature of skin when cooled by said
surface, the device being designed so that the value of the thermal
resistance, the heat sink means temperature, and the area of the
heat collecting surface maximize the skin temperature difference
for different perfusion rates.
2. The device as set forth in claim 1 wherein said means for
measuring the temperature of skin tissue is a temperature sensing
device within the said heat collecting disc having means for
connecting said temperature sensing device to a means for
displaying the temperature.
3. The device as set forth in claim 2 wherein said temperature
sensing device is a thermocouple.
4. The device as set forth in claim 2 wherein said temperature
sensing device is a thermistor.
5. A device for diagnosing tumors and circulatory disorders by
determining the perfusion rate of superficial skin tissue by
measuring the temperature of skin after the superficial tissue has
been cooled below its normal temperature comprising:
a flat heat collecting surface having a defined area which can be
placed in thermal communication with the skin and enable heat
transfer from the skin to said heat collecting surface;
a vessel for containing a coolant which functions as a heat sink
for cooling said heat collecting surface to enable the superficial
tissue to be cooled below its normal temperature when said heat
collecting surface is placed in thermal communication with the
skin;
a coolant in said vessel;
a thermal resistance in the heat flow path between said heat
collecting surface and said coolant including spacer means for
defining the height of said thermal resistance, said coolant
cooling said heat collecting surface through said thermal
resistance to a steady state temperature above the temperature of
the coolant; and,
means for measuring the temperature of skin when cooled by said
surface, the device being designed so that the value of the thermal
resistance, the heat sink temperature, and the area of the heat
collecting surface maximize the skin temperature difference for
different perfusion rates.
6. The device as set forth in claim 5 wherein said means for
measuring the temperature of skin tissue is a temperature sensing
device within the said heat collecting disc having means for
connecting said temperature sensing device to a means for
displaying the temperature.
7. The device as set forth in claim 6 wherein said temperature
sensing device is a thermocouple.
8. The device as set forth in claim 6 wherein said temperature
sensing device is a thermistor.
9. The device as set forth in claim 6 also including a heat
distributor in thermal communication with said resistance and said
coolant.
10. The device as set forth in claim 9 wherein said heat collecting
disc contains copper.
11. The device as set forth in claim 6 wherein said heat collecting
disc is inclusive of a heat conducting inner disc, an outer ring of
a heat conducting material and an insulating ring between said
outer ring and said inner disc, With the temperature sensing device
being positioned within said inner disc to maximize the penetration
depth of said heat collecting surface while maximizing the device's
sensitivity to small tumors.
12. A device for diagnosing tumors and circulatory disorders by
determining the perfusion rate of superficial skin tissues by
measuring the temperature of skin after the superficial tissue has
been cooled below its normal temperature comprising:
a heat collecting disc having a flat heat collecting surface having
a defined area which can be placed in thermal communication with
the skin and enable heat transfer from the skin to said heat
colleting surface;
a vessel for containing a coolant which functions as a heat sink
for cooling said heat collecting surface to enable the superficial
tissue to be cooled below its normal temperature when said heat
collecting surface is placed in thermal communication with the
skin;
a coolant in said vessel;
a heat distributor in thermal communication with said coolant;
a spacer ring between said heat distributor and said heat
collecting disc, said spacer ring defining the height of a column
of liquid between said heat distributor and said heat collecting
disc to provide a thermal resistance in the heat flow path between
said heat collecting surface and said coolant, said coolant cooling
said heat collecting surface through said thermal resistance to a
steady state temperature above the temperature of the coolant;
and,
means for measuring the temperature of skin when cooled by said
surface, the device being designed so that the value of the thermal
resistance, the heat sink temperature, and the area of the heat
collecting surface maximize the skin temperature difference for
different perfusion rates.
13. The device as set forth in claim 12 wherein the coolant is ice
water and said spacer ring defines a column of water.
14. The device as set forth in claim 13 wherein said spacer ring is
dimensioned to result in a resistance such that the equilibrium
temperature of normal tissue cooled with said device is
approximately 15.degree.C.
15. The device as set forth in claim 14 wherein said heat
collecting disc is inclusive of a heat conducting inner disc, an
outer ring of a heat conducting material and an insulating ring
between said outer ring and said inner disc, said inner disc,
insulating ring and outer ring being in thermal communication with
said thermal resistance.
16. The device as set forth in claim 15 wherein said means for
measuring the temperature of skin tissue is a temperature sensing
device located in said inner disc.
17. The device as set forth in claim 16 wherein said inner disc is
formed of copper.
18. The device as set forth in claim 17 wherein said temperature
sensing device is a thermistor.
19. The device as set forth in claim 18 wherein said outer ring is
formed of copper.
20. A method for diagnosing the presence of human tumors and
circulatory disorders comprising the following steps:
A. applying a flat cooling surface to the skin to be diagnosed and
cooling the skin through a thermal resistance of a known value
which is in thermal communication with a heat sink at a known
constant temperature to a steady state temperature below normal
skin temperature and above the temperature of the heat sink.
B. measuring the temperature of the skin cooled in Step A after a
temperature equilibrium is reached between the skin and the cooling
surface; and
C. comparing the temperature of the skin measured in Step B with a
standard to determine the presence of tumors or circulatory
disorders beneath the skin by comparing the perfusion rates which
are deduced from the cooled skin temperature, the sink temperature
and the value of the thermal resistance.
21. The method as set forth in claim 1 wherein the temperature of
the skin is measured in Step B by measuring the temperature of the
cooling surface.
22. The method as set forth in claim 21 wherein in Step A the skin
is cooled to a temperature of about 15.degree.C.
Description
BACKGROUND OF THE INVENTION
The present invention relates to the diagnosis of tumors by
measuring the temperature of skin tissue where tumors are suspected
and comparing this temperature with a standard taken for normal
tissue, which is usually at a contra-lateral position. As used
throughout this specification and claims, the term "contralateral"
postition is intended to represent a position of the body that is
bi-laterally symmetrical to another position of the body. For
example, the right ear is in a position in the human body
contralateral to the left ear. A thermal method similar to the
foregoing method of diagnosis for determining the presence of
cancerous tumors is known. This known method is commonly referred
to as infra-red thermography. Other methods for diagnosing the
presence of tumors include mammography and xerography. Since
mammography and xerography have well known disadvantages and bear
little resemblence to the present method and device, they are not
discussed further.
Infra-red thermography has been used with some success for the
differential diagnosis of a variety of tumor masses which lie near
to the skin surface. Such diagnoses are based upon differences in
skin temperatures between cancerous and healthy tissue. Perhaps the
most significant deficiencies associated with infrared thermography
are the problems of interpreting marginal readings and the high
cost associated with infra-red systems. Another deficiency of
infra-red thermographic devices is that they are not operated in
conjunction with any detailed analysis of thermal parameters.
Indeed, infra-red thermography is not practiced in an efficient
manner.
SUMMARY OF THE INVENTION
The deficiences of prior art methods and devices for detecting
tumors are significantly reduced by the method and device of the
present invention which utilizes a discovery that the skin
temperature difference between cancerous and healthy tissue is
determined for the most part by the perfusion rate of blood in the
tissue and that perfusion rates through cancerous tissue can differ
significantly from perfusion rates through healthy or normal tissue
during conditions of moderate cooling. In accordance with the
present invention, the temperature difference between cancerous and
healthy tissue is enhanced by cooling small areas of tissue through
a thermal resistance which maximizes the sensitivity of the method
and devices for detecting the presence of tumors.
Accordingly, it is an object of the present invention to provide a
new and improved method and device for the differential diagnosis
of human tumors lying near to the skin's surface.
It is a further object of the present invention to provide a method
and device for diagnosing the presence of tumors and circulatory
disorders which is more economical than known prior art methods and
devices.
It is a further object of the present invention to provide a method
and device for diagnosing the presence of tumors which indirectly
measures and compares the difference between the perfusion rate of
healthy tissue and cancerous tissue.
It is a further object of the present invention to provide a device
which can be used to cool the surface of cancerous tissue and
measure the temperature of the tissue cooled so that the measured
temperature can be compared to a standard.
A further object of the present invention is to provide a method
and device with which temperature differentials between cancerous
and normal tissue of a few degrees centigrade can be determined to
diagnose the presence of tumors.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a perspective view of the device for measuring the skin
temperature difference between cancerous and normal tissue;
FIG. 2 is a horizontal sectional view taken along line 2--2 of FIG.
1;
FIG. 3 is a vertical sectional view taken along line 3--3 of FIG.
1;
FIG. 4 is an exploded perspective view of a heat collecting disk,
spacer, baffle and finned distributor of the temperature measuring
device in accordance with the present invention;
FIG. 5 is a schematic diagram illustrating local cooling of the
section of skin tissue with an isothermal heat collecting disk in
accordance with the present invention;
FIG. 6 is a graph showing the temperature of skin subjected to
local cooling with a heat collecting disk of radius a in accordance
with the present invention;
FIG. 7 is a graph showing the value for an optimum resistance
(dimensionless) in accordance with the present invention;
FIG. 8 is a graph showing the affect of the radius of a heat
collecting disk on the sensitivity of a device in accordance with
the present invention;
FIG. 9 is a schematic diagram showing the penetration region for a
one-piece heat collecting disk in accordance with the present
invention; and
FIG. 10 is a schematic diagram showing the penetration region for a
three-piece heat collecting disk in accordance with the present
invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
At the outset, the method and device of the present invention is
described in its broadest overall aspects with more detailed
descriptions following. The present invention is based on the
discovery that the skin temperature difference between cancerous
and healthy tissue under conditions of cooling is mainly determined
by the blood perfusion rate in the tissue and, most importantly,
that the temperature difference may be enhanced by increasing the
thermal interaction with the environment. Increasing the thermal
interaction with the environment may be accomplished by either
lowering the environmental temperature or by optimizing the surface
heat transfer conditions.
In accordance with the present invention, localized cooling is
employed which permits large temperature differences between
cancerous and healthy tissues to be obtained without excessive heat
loss from the patient. It should be noted that excessive heat loss
can result in deleterious effects. For example, if heat loss is
great, patient comfort is affected. Indeed, physiological
responses, such as shivering, may be induced by large heat losses
which are detremental to the measurement procedure. It is for the
foregoing reasons that the enhancement in temperature differences
which can be achieved by infra-red thermography is limited. With
the device and method of the present invention, the cooling area is
small when compared to the area associated with infra-red
thermographic methods.
At this point, it should be noted that the concept of localized
thermal interaction with tissue is not new, but with previous
analysis utilizing localized thermal interaction with the tissue,
an understanding of the significance of the observed effects was
not known.
As is stated above, the method and device of the present invention
is predicated on the fact that the growth of human tumors is
normally accompanied by changes in local blood perfusion and
metabolic rates. In general, these changes affect temperature
distributions in the vicinity of tumors. Thus, differential
diagnoses of tumors can be made from observations on temperature
fields around tumors and in corresponding (usually contra-lateral)
healthy tissues. Prior to the present invention, temperature
variations have been observed at the skin for superficial tumors,
i.e., tumors at or below the skin. Indeed, prior to the present
invention, breast cancer has been successfully diagnosed by
observing "abnormal" thermal patterns at the skin.
In principle, the thermal patterns within tissue are affected not
only by the perfusion and metabolic rates but also by the surface
thermal conditions in the proximity of the region of interest.
Thus, it is important to state the surface heat transfer conditions
(i.e., cooling, heating, or insulation) under which the thermal
pattern is observed.
To demonstrate the method of the present invention, the laboratory
device as set forth in FIGS. 1-4 was constructed. At this point, it
should be noted that the device shown in FIGS. 1-4 was constructed
in the laboratory with parts that were readily available. The
significance of the foregoing is that it should be readily apparent
that modifications might be made on the device shown in FIGS. 1-4
when commercial instruments in accordance with the present
invention are manufactured and sold. Thus, the description which
follows relating to the device shown in FIGS. 1-4 is not intended
to limit the invention in any way, but is offered primarily to show
the advance in the art which has resulted from the present
invention.
FIG. 1 is a perspective view of a device 10 in accordance with the
present invention for measuring the perfusion rate of skin tissue.
The purpose of the device is to cool an area of tissue to be
diagnosed and to measure the temperature at the skin's surface
after the tissue has been cooled. To accomplish the foregoing,
device 10 is inclusive of a vessel 12 which can hold a quantity of
ice and water which serves as a heat sink. Vessel 12 is insulated
by a layer of urethane foam insulation 14 which has foil faces 16.
Vessel 12 is water tight and is formed from an organic plastic
material such as the material sold under the trade name
Plexiglas.
Hermetically sealed to the bottom of vessel 12 is a heat collecting
disk 18. It has been found advantageous to form a major portion of
the volume of heat collecting disk 18 from copper since copper is a
highly thermally conductive material which is available at a
reasonable cost; however, other materials are suitable for forming
a collecting disk. As will be apparent to those skilled in this art
from the discussion which follows, the most important property for
consideration in choosing a material for heat collecting disk 18 is
the thermal conductivity of that material.
For the reasons which are explained in greater detail below, it has
been found advantageous to thermally insulate the copper material
which forms the central portion of heat collecting disk 18 from the
copper on the outer portion of heat collecting disk 18. To
accomplish the foregoing insulation, disk 18 is fabricated in three
sections which include an outer ring 20 which is formed of copper,
an insulating ring 22 which is formed of material such as Plexiglas
plastic, and an inner disk 24 which is also formed of copper (see
FIGS. 3 and 4). The foregoing sections may be held together by a
friction fit or they may be glued to form a disk-like
structure.
When device 10 is to be used to diagnose the presence of tumors, it
is filled with ice water 26. To allow heat collecting disk 18 to
conduct heat away from skin tissue toward the heat sink (ice water
26), device 10 is provided with a distributor 28. To increase
thermal communication between ice bath 26 and collecting disk 18,
distributor 28 includes an upper finned section 30 and a lower
cylindrical section 32. It has been found advantageous to form
distributor 28 out of aluminum because of the low weight and high
conductivity associated with aluminum. As will be apparent to those
skilled in this art, however, other materials and other components
can be employed to provide the function of distributor 28 which is
a means for increasing thermal communication between the heat
collecting disk and the heat sink (ice bath 26) or as a means for
transfering thermal energy between the cooling surface (collecting
disk 18) and the heat sink.
The skin tissue being diagnosed is cooled to a temperature below
the temperature which results when a patient is in a room at room
temperature (20.degree.C). At this point, it should be noted that
if the heat collecting disk 18 were to contact distributor 28, the
result would be unacceptable. The reason for this fact is that the
thermal conductivity of copper and aluminum is so high that the
skin being diagnosed would reach a temperature close to the
temperature of the sink (ice bath). Therefore, in accordance with
the present invention, skin being diagnosed is cooled through a
resistance (R). In the device of FIGS. 1-4, that resistance (R) is
the result of a separation and insulation between the bottom of
cylindrical section 32 of distributor 28 and collecting disk 18.
Although many materials and components are suitable for providing a
resistance (R), it has been found advantageous to separate
distributor 28 from collecting disk 18 with a spacer ring or collar
34 and to fill the chamber formed by the inner volume of the spacer
ring with a spacer insulator 36 (see FIGS. 3 and 4). Because ice
water is used as a heat sink, it is economical to use water as the
spacer insulator material 36. One reason for using water is that
its use as an insulator does not require a seal between the
insulator material and ice bath. Thus, with water being used as the
spacer insulator, only one hermetical or water tight seal is
necessary in the device. As is set forth above, that seal is
between the collecting disk 18 and the vessel 12. When water is
used as an insulator, spun glass is inserted into the water gap as
a baffle 33 to prevent natural convection. The spun glass or glass
wool has a low volume fraction and does not contribute
significantly to the effect of the resistance.
In the theoretical discussion which follows, the importance of
providing a resistance between the heat collector and the heat sink
is set forth. In that discussion, the effect of the value of the
resistance is also set forth. At this point, however, it should be
noted that the value of the resistance is proportional to the
thickness of the resistance for resistances of constant radii. In
the device shown in FIGS. 1-4, the resistance is proportional to
the thickness of the water gap. Thus, with the device of FIGS. 1-4,
the value of the resistance can be easily increased or decreased by
changing the height of spacer ring or collar 34.
As is apparent from the foregoing, the ice bath 26 in vessel 12
will cool collecting disk 18 because thermal energy will flow from
collecting disk 18 into the ice bath. Collecting disk 18 will in
turn cool the skin tissue to which it is applied because heat will
flow from the skin tissue into the heat collecting disk 18. Of
course, blood flow in blood vessels within the cooled tissue will
counteract the heat loss caused by the heat collecting disk 18.
This blood flow or perfusion rate will vary according to whether or
not the tissue is normal tissue or tissue containing tumors.
Different perfusion rates between cancerous and normal tissues
results in skin temperature readings which differ between cancerous
and normal tissues.
As is best shown in FIG. 3, collecting disk 18 is provided with a
thermistor 38. The temperature of the disk 18 which approximately
equals skin temperature (T.sub.skin) is thus measured with the
thermistor 38.
During fabrication of device 10, thermistor 38 is introduced into
collecting disk 18 through a bore applied for that purpose.
Thermistor 38 is placed within inner disk 24 so that temperatures
can be measured from that portion of collecting disk 18. The
thermistor 38 is connected to a meter or read out (not shown). It
has been found advantageous to use a digital type read out which
measures temperatures to 1/10 of 1.degree.C. At this point, it
should be noted that other temperature measuring schemes can be
used in the device of the present invention such as, for example, a
thermocouple. These features, however, are well understood by those
in this art.
The overall dimensions of the device shown in FIGS. 1-4 are as
follows. The overall vertical height of device 10 from the bottom
of heat collecting disk 18 to the top of vessel 12 is 10.2 cm. The
outside diameter of the upper part of vessel 12 is 7.75 cm. The
outside diameter of collecting disk 18 is 2.54 cm. Device 10 when
filled with ice water weights about one-half kilogram. About ten
minutes is required to reach thermal equilibrium with the tissue
being diagnosed. Device 10 can be operated for about 30 minutes
without requiring replacement of the heat sink (ice bath).
A theoretical discussion of the present invention has been
presented in two papers at the Second International Symposium on
Cancer Detection and Prevention in Bologna, Italy, on Apr. 9-12,
1973. The papers are entitled "A New Thermal Method for the
Differential Diagnosis of Human Tumors" by John Cary, Borivoje
Mikic and Richard Johnson and "A Thermal Analysis of Human Tissue
with Applications to Thermography" by John Cary and Borivoje Mikic.
The teachings of the foregoing two papers are incorporated herein
by reference. The foregoing papers are available to the public on
request by writing to:
Cesare Maltoni, Secretary General International Study Group on
Detection and Prevention of Cancer Secretariat: Instituto di
Oncologia "F Addarii" Viale Ercolani 4/2 40138 Bologna, Italy
The important teachings of the foregoing publications appear in the
theoretical discussion below.
The theory upon which the method and device of the present
invention is based is set forth below and is illustrated in FIG. 5
where a disk of radius, a, and uniform temperature, T.sub.S, in
contact with the skin is shown. The disk is assumed to be at a
uniform temperature and is made of highly thermally conductivity
material such as copper. The temperature of the disk (and of the
skin, also, since the skin and the disk are in intimate contact)
is: ##SPC1##
where R is the thermal resistance between the heat sink (at
temperature T.sub.O) and the disk (at temperature T.sub.S), T.sub.A
is the arterial blood temperature, k is the tissue thermal
conductivity, W.sub.b is the blood perfusion rate, C.sub.b is the
specific heat of blood, and Q.sub.M is the metabolic heat
generation. In the c.g.s. system, R has the units [cm.sup.2
sec.degree.C/cal], T [.degree.C], k [cal/cm/sec/.degree.C], w.sub.b
[gm/cm.sup.3 /sec], c.sub.b [cal/gm/.degree.C], Q.sub.M
[cal/cm.sup.3 /sec], and a [cm]. Also, .lambda. =.sqroot.w.sub.b
c.sub.b /k. I, a dimensionless function of a and .lambda., is a
derived integral. .lambda. has units [cm.sup..sup.-1 ] and
1/.lambda. and may be thought of as a characteristic thermal
distance. Although .lambda. is proportional to .sqroot.w.sub.b, it
is used interchangeably with perfusion rate. Rk/a and a.lambda. are
dimensionless groups which make it convenient to analyze the
problem in general terms. R and a are the variables of interest
which are characteristic of the device of the present
invention.
FIG. 6 shows T.sub.S as a function of perfusion rate, assuming
Q.sub.M /w.sub. b c.sub.b is constant for a given tissue. This is
probably a better assumption for healthy tissues, where oxygen
demand can have auroregulatory control over local perfusion than
for tumors, for which the mechanisms are not as well understood.
However, during an ongoing study of the vascular states of tumors
undergoing radiation therapy, it was discovered that the adiabatic
tumor temperature was never more than 1.degree.C above mouth
temperature. From this fact, it was estimated that Q.sub.M /w.sub.b
c.sub.b is on the order of 1.degree.C or less. Moreover, since
T.sub.A - T.sub.O is much greater than one, Q.sub.M [ w.sub.b
c.sub.b (T.sub.A - T.sub.O)] is much less than one. Therefore, the
results are not strongly affected by the assumption, and, in fact,
under the cooling conditions used, one does not introduce
significant error by neglecting the effect of metabolism
altogether.
In view of the foregoing, a typical system utilizing ice water for
its heat sink was considered and its response examined in terms of
perfusion rates and thermal resistance. Under conditions of
cooling, mainly due to the lack of vasoconstriction mechanisms in
tumors, the perfusion rates in healthy tissues can be considerably
less than in tumors. Indeed, perfusion rates measured with a local
cooling method indicated, for example, that in tumors,
.lambda..sub.T = 2 cm.sup..sup.-1 and in healthy tissue,
.lambda..sub.N = 0.5 cm .sup.-.sup.1. (Here, T = tumor, and N =
normal or healthy.)
If the radius of the disk of a typical system is 1 cm, it is
possible to calculate the response of the device. For example, if
the perfusion rates in the cancerous and healthy tissue are as
described above, then a.lambda..sub.N = 0.5 and a.lambda..sub.T =
2. From FIG. 6 it is seen that the temperature difference which
would be observed when the disk is placed first on cancerous and
then on healthy tissue, it is very much dependent upon the value of
the thermal resistance, R, which controls the heat flow from the
skin to the heat sink. For Rk/a = 0.44, the skin temperature
difference, .DELTA.T.sub.S, is 6.degree.C, while if Rk/a = 0.044 or
4.4, the temperature difference is only about 2.degree.C. It is
evident that there exists an optimum thermal resistance for which
one would obtain a maximum temperature, .DELTA.T.sub.S, between
cancerous and healthy tissue.
An expression for the optimum value of R, which induces the maximum
skin temperature difference between healthy and cancerous tissue,
was derived as follows: ##EQU1## Equation (2) is plotted (in
dimensionless form) in FIG. 7 for differential changes in the
perfusion rate. A good aproximation is to let .lambda.
=.sqroot..lambda..sub.T .lambda..sub.N and evaluate R.sub.opt from
FIG. 7. If R is within a factor of two of R.sub.opt, the
temperature difference obtained will not be much less than the
maximum. It can be shown that (Rk/a).sub.opt = 0.44 for the
previous example; thus, the 6.degree.C temperature difference
obtained is the absolute maximum for those assumed perfusion rates
and a radius of 1 cm.
For a heat sink temperature of 0.degree.C, the maximum temperature
difference which can be induced between cancerous and healthy
tissue (with the assumed perfusion rates .lambda..sub.T = 2
cm.sup.-.sup.1 and .lambda..sub.N = 0.5 cm.sup.-.sup.1) is
12.3.degree.C. Thus, a disk of radius 1 cm is only about 50 percent
as sensitive as the theoretical maximum. The loss in sensitivity is
due to the small disk size. FIG. 8 shows that as the disk radius
goes to infinity, the sensitivity of the device approaches the
theoretical maximum; for small disks (radii less than 1 cm), the
sensitivity falls towards zero very rapidly.
The loss of sensitivity (for this particular example) is not very
crucial since the 6.degree.C temperature difference which would be
obtained is still much greater than that normally obtained in
thermography. However, for small differences in the perfusion rate
between healthy and cancerous tissue, or for tumors separated from
the surface by a layer of normal tissue, the loss of sensitivity
due to the small disk radius would be substantial. This loss is
caused by a reduction in the penetration depth (e.g., the depth
from where heat energy originates which flows into the disk). The
concept of penetration depth is illustrated in FIG. 9. Furthermore,
for a small tumor within the region of penetration, the
contribution to the overall heat flowing from the tumor through the
disk is small; thus, the sensitivity of the disk to small tumors
will be small.
The concept of penetration depth suggests as large a disk as is
possible, but the inability to detect small tumors, and the
drawback of large heat loss from the patient for large disks,
favors the opposite. However, it is clear that (1) the center of
the disk in FIG. 9 has a penetration depth which is near that of
the maximum penetration depth (for very large disk radii) and which
is much larger than the average penetration depth, and (2) the heat
that flows through this center portion comes from a small region.
Hence, if the center part of the disk is thermally insulated from
the outer annulus, then the center portion of the disk will have a
penetration depth as if it were very large, but it will also be
sensitive to small tumors since the heat which comes to the center
portion comes from a small region. The foregoing is illustrated in
FIG. 10. For the foregoing reasons, the heat collecting disk 18
(see FIGS. 3 and 4) was made with an insulated center portion 22,
and the temperature is measured there, independent of the outer
annulus or ring 20.
In the laboratory device which was constructed in accordance with
the present invention and which included the three-piece heat
collecting disk shown in FIGS. 3 and 4, the outside diameter of
outer ring 20 was approximately 2.54 cm. The diameter of inner disk
24 was approximately 1.00 cm. Inner disk 24 was separated from
outer ring 20 by insulating ring 22 which was approximately 0.26 cm
thick. Thus, the outside diameter of insulating ring 22 was
approximately 1.52 cm.
EXPERIMENTAL RESULTS
Operating procedure is to place the device on the skin over a
suspected tumor (determined either by palpation, thermography,
mammography, or some other means) and then on a symmetric normal
area. (Of course, two identical instruments could be used
simultaneously.) When the steady-state is reached, after five to
ten minutes, the heat collecting disk (i.e., skin) temperatures are
recorded. The diagnosis is based on the difference between these
two readings, the same as for thermography.
The proper value for R (i.e., the water gap thickness) can be
determined in a number of ways. One way is to adjust the value of R
when the device is in contact with normal tissue so that the
steady-state temperature is about 15.degree.C. Another is, of
course, from experience. A third way is to set the water gap
thickness equal to [(conductivity of water)/k] cm.
Experimental evidence has been compiled from perfusion measurements
on tumors undergoing radiation therapy. From these observations,
the response of a relatively insensitive one-piece disk was
calculated (see Table 1). Over 6.degree.C temperature difference
can be obtained with large tumors. A small parathyroid tumor would
be 1.2.degree.C difference between the region directly over the
tumor and contra-lateral normal tissue.
Calculations for the device of FIGS. 1-4 with the threepiece disk
18 (i.e., thermally insulated center portion 22) indicate that
large tumors with similar perfusion rates will yield more than
10.degree.C temperature difference, and small tumors within the
region of penetration could show temperature differences of a few
degrees centigrade.
TABLE 1 ______________________________________ Temperature
Differences Calculated From Perfusion Measurements Between
Cancerous and Healthy Tissue Before and During Radiation Therapy
(One-Piece Disk, Radius = 1.5 cm)
______________________________________ Skin Temperature Tumor
Location Tumor Size Difference
______________________________________ Groin 100 cm.sup.3
8.0.degree.C Breast 120 4.1 do. 7.2 do. 6.2 do. 8.4 75 4.4 do. 7.6
do. 5.1 do. 5.4 do. 5.6 40 3.0 do. 5.5 do. 6.3 do. 6.2 18 7.6 Neck
30 1.0 1.1 Parathyroid 1 (?) 1.2
______________________________________
In accordance with the objects of the present invention, a new and
improved thermal method and device for the differential diagnosis
of human tumors has been achieved. The device of the present
invention maximizes skin temperature differences between cancerous
and healthy tissue. The new device, in accordance with the present
invention, includes a heat sink, a thermal resistance, a small heat
collecting surface which can touch and cool a patient's skin and a
means for measuring the temperature of the cooled skin.
By following the teachings of the present invention, surface
temperature changes of superficial tissue due to blood perfusion
changes can be substantially increased to facilitate diagnosing the
presence of cancerous tissue or circulatory disorders.
The invention may be embodied in other specific forms without
departing from the spirit or essential characteristics thereof. The
present embodiments are therefore to be considered in all respects
as illustrative and not restrictive, the scope of the invention
being indicated by the appended claims rather than by the foregoing
description, and all changes which come within the meaning and
range of equivalency of the claims are therefore intended to be
embraced therein.
* * * * *